ArticleNature physics2023
Enhanced statistical sampling reveals microscopic complexity in the talin mechanosensor folding energy landscape.
Article in Nature physics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Molecular dynamics simulations reveal DNA gate opening mechanisms for M. smegmatis topoisomerase 1A.Biophysical journal · 2026Article
- The local mechanostructural properties of protein cargoes regulate nucleocytoplasmic transport.Nature physics · 2026Article
- Force writes memory: proline isomerization as a molecular memory switch.Biochemical Society transactions · 2025Review
- Single-molecule magnetic tweezers to unravel protein folding dynamics under force.Biophysical reviews · 2025Review
- Analytical methods in studying cell force sensing: principles, current technologies and perspectives.Regenerative biomaterials · 2025Review
- Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing.Science advances · 2024Article
- Universal cold RNA phase transitions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Learning noise-induced transitions by multi-scaling reservoir computing.Nature communications · 2024Article
- Molecular dynamics simulations reveal how vinculin refolds partially unfolded talin rod helices to stabilize them against mechanical force.PLoS computational biology · 2024Article
- Single-molecule magnetic tweezers to probe the equilibrium dynamics of individual proteins at physiologically relevant forces and timescales.Nature protocols · 2024Review
- Identical sequences, different behaviors: Protein diversity captured at the single-molecule level.Biophysical journal · 2024Article
- A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Folding kinetics of an entangled protein.PLoS computational biology · 2023Article
- Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins.eLife · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Statistical mechanics can describe the major conformational ensembles determining the equilibrium free-energy landscape of a folding protein. The challenge is to capture the full repertoire of low-occurrence conformations separated by high kinetic barriers that define complex landscapes. Computationally, enhanced sampling methods accelerate the exploration of molecular rare events. However, accessing the entire protein's conformational space in equilibrium experiments requires technological developments to enable extended observation times. We developed single-molecule magnetic tweezers to capture over a million individual transitions as a single talin protein unfolds and refolds under force in equilibrium. When observed at classically-probed timescales, talin folds in an apparently uncomplicated two-state manner. As the sampling time extends from minutes to days, the underlying energy landscape exhibits gradually larger signatures of complexity, involving a finite number of well-defined rare conformations. A fluctuation analysis allows us to propose plausible structures of each low-probability conformational state. The physiological relevance of each distinct conformation can be connected to the binding of the cytoskeletal protein vinculin, suggesting an extra layer of complexity in talin-mediated mechanotransduction. More generally, our experiments directly test the fundamental notion that equilibrium dynamics depend on the observation timescale.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.